S9: cortical dysfunction Flashcards
Define dementia
Umbrella term for loss of memory and other thinking abilities severe enough to interfere with daily life
Result of the progressive destruction of neurones
Describe ‘plaques’ in Alzheimer disease
Amyloid precursor protein helps to repair neurones following damage
Alpha and gamma secretase normally chop it up for disposal into soluble parts
However, if beta secretase gets involved, the resulting parts of APP are no longer soluble
Insoluble peptides accumulate outside the cell -> beta amyloid plaques: fill space between neurones & reduce signal transmission
What can plaque formation result in?
Can induce an inflammatory response, causing neuronal death
Plaques deposit around blood vessels
-amyloid angiopathy can occur
-weakened blood vessels can bleed
Describe ‘tangles’ in Alzheimer disease
Tau proteins play a role in stabilising microtubules with the neuronal cytoskeleton
Beta amyloid plaques induce pathological processes within the neuron -> results in hyperphosphorylation of Tau proteins
Causes a change in shape of Tau proteins, no longer able to support cytoskeleton
Neurone death, also aggregate together into tangles
Outline macroscopic changes which occur in Alzheimer disease
General brain atrophy Narrowing of gyri Widening of sulci Ventricular enlargement Hippocampus often affected first
Describe the role of acetylcholine in Alzheimer’s
ACh concentration and function is decreased in patients
Certain Alzheimer’s medications target this problem – acetylcholinesterase inhibitors
Outline the types of Alzheimer disease
Sporadic – causes poorly understood, prevalence increases with age
Familial – early onset dementia, PSEN ½ genes implicated (mutation of gamma secretase), trisomy 21
List symptoms of Alzheimer disease
Initially symptoms hard to detect Short term memory often lost first Motor and language skills affected Long term memory loss Disorientation Immobilisation is linked to cause of death – pneumonia
Outline the diagnosis of Alzheimer disease
Are any medications responsible? Any other disease processes causing symptoms? E.g. hypothyroidism, hypercalcaemia, B12 deficiency, normal pressure hydrocephalus, exclude delirium CT scan – show macroscopic changes Brain biopsy (postmortem) is only definitive method
Describe the treatment for Alzheimer’s
No cure
Acetylcholinesterase inhibitors
Memantine (for advanced cases) – glutamate receptor antagonist
Describe Lewy body dementia
Dementia like features early
Parkinsonian features later
Occurs 50-85 years old
More rapid progression
What is the pathogenesis of Lewy body dementia?
Caused by misfolding of protein called alpha-synuclein
These misfolded proteins aggregate into Lewy bodies
Main sites of deposition are:
1) Cortex: dementia like symptoms
2) Substantia nigra: parkinsonian features
List symptoms and treatment of Lewy body dementia
Cognitive symptoms: distressing hallucinations, depression, REM sleep disorders
Parkinson’s symptoms (later): bradykinesia, resting tremor, stiffness
Treatment: symptom based & levodopa (dopamine analogue)
Describe frontotemporal lobe dementia
Aggregated proteins (inclusion bodies) – often younger patients & Tau protein hyperphosphorylation
Affects frontal and temporal lobe
Frontal lobe – behavioural and emotional changes, disinhibition (hostility)
Temporal lobe – language impairment (progressive aphasia)
Describe vascular dementia
Heterogenous dementia & can affect multiple sites in brain
Presentation related to area of brain affected
Caused by multiple infarcts and ischaemia -> atherosclerosis, emboli, hypertension & vasculitis
Treatments target risk factors
Describe HIV and AIDS dementia
Cause poorly understood Damage caused by virus itself Viral proteins cause injury/inflammation Result is neuron damage AIDS dementia complex can affect behaviour, memory, thinking and movement
Describe delirium
An acute, fluctuating syndrome of disturbed consciousness, attention, cognition and perception
Presents suddenly
Categorised as:
1) Hyperactive – agitated/aggressive, delusions
2) Hypoactive – drowsy/withdrawn
List the causes of delirium
Drugs Epilepsy/electrolyte imbalance Liver failure/low oxygen Infection Retention Intracranial Uraemia Metabolism
Describe the treatment for delirium
Minimise/treat precipitating factors
Encourage normal day/night cycle
Allow wandering
For challenging behaviours – distraction techniques
Medications last resort (ie. Haloperidol)
List primary causes of headaches
Non-‘life or sight’ threatening, many chronic
Tension-type headache
Migraine
Cluster headache
List secondary causes of headaches
Space-occupying lesion Haemorrhage Meningitis Giant cell arteritis Trigeminal neuralgia Medication-overuse
List red flags for headaches
Systemic signs and disorders
Neurologic symptoms
Onset new or changed & patient > 50 years old
Onset in thunderclap presentation
Papilloedema, positional provocation & precipitated by exercise
Describe tension-type headache
F>M, common, young and young adults
Pathophysiology thought to be due to tension in muscles of head and neck
Generalised – predilection for frontal and occipital regions
Tight/band like, constricting +/- radiating into neck, worse at end of day, recurrent
Triggers: stress, poor posture, lack of sleep
Often responds to simple analgesics
Describe migraines
F>M, common, presents early to mid-life
Pathophysiology unclear, possible theories proposed:
1) Neurogenic inflammation of trigeminal sensory neurones innervating large vessels and meninges
2) Alters way pain processed by brain; sensitised to otherwise ignored stimuli
Describe the presentation of migraines
Unilateral, temporal or frontal, throbbing, pulsating
Often disabling (need to lie down)
Prolonged headache
Triggers: certain food, menstrual cycle, stress, lack of sleep, strong familial links
Associated symptoms: photophobia, phonophobia, nausea, aura
Describe medication over-use headache
F>M, 30-40 year old
Headache present on at least 15 days/month, occurs in patients with pre-existing headache disorder
Using regular analgesics – headache not responding
Variable character, co-exists with depression & sleep disturbance
Discontinue medication (typically resolved completely by 2 months)
Describe cluster headaches
M>F
Smoking history major risk factor
Usually begins 30-40 years
Pathophysiology unknown
Describe the presentation of a cluster headache
Unilateral, around or behind eye
Severe, intense, often disabling, agitated
Occurs in clusters with periods of remission
Triggers: alcohol, cigarettes, volatile smells, warm temp, lack of sleep
Simple analgesics often ineffective
Ipsilateral autonomic symptoms (red, watery eye, blocked runny nose, ptosis)
Describe the presentation of a space-occupying lesion
Gradual, progressive
Worse in mornings
Worsened with posture, cough, Valsalva manoeuvre, straining
Nausea, vomiting, focal neurological or visual symptoms
Clinical exam: focal (unilateral) neurological signs, papilloedema
Describe trigeminal neuralgia
F>M
50-60 years
Most caused by compression of CN V due to loop of a blood vessel
5% due to tumours/skull base abnormalities or AV malformations
Describe the presentation of trigeminal neuralgia
Unilateral, pain felt in > 1 divisions of CN V
Sharp, stabbing, ‘electric’ shock
Sudden onset
Triggers: light touch to face/scalp, eating, cold wind, combing hair
Simple analgesics not effective, can be difficult to treat
Describe temporal arteritis
Vasculitis of large and medium sized arteries of head
F>M, > 50 years
Consider in any >50 year old with abrupt onset of headache & visual disturbance/jaw claudication
Superficial temporal artery commonly involved
Risk of irreversible loss of vision due to involvement of blood vessels supplying CN II
